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Ingestible chip could help diagnose disease

MIT researchers have built an ingestible sensor equipped with genetically engineered bacteria that can diagnose bleeding in the stomach or other gastrointestinal problems.

This ‘bacteria-on-a-chip’ approach combines sensors made from living cells with ultra-low-power electronics that convert the bacterial response into a wireless signal that can be read by a smartphone.

“By combining engineered biological sensors together with low-power wireless electronics, we can detect biological signals in the body and in near real-time, enabling new diagnostic capabilities for human health applications,” says Associate Professor Timothy Lu of MIT.

The researchers say they were able to create sensors that respond to heme, a component of blood, as well as sensors that could respond to a molecule that is a marker of inflammation.

Synthetic biologists have made great strides in engineering bacteria to respond to stimuli such as environmental pollutants or markers of disease. These bacteria can be designed to produce outputs such as light when they detect the target stimulus, but specialised lab equipment is usually required to measure this response.

To make these bacteria more useful for real-world applications, the MIT team combined them with an electronic chip that could translate the bacterial response into a wireless signal.

“Our idea was to package bacterial cells inside a device,” Assoc Prof. Nadeau adds. “The cells would be trapped and go along for the ride as the device passes through the stomach.”

For their initial demonstration, the researchers focused on bleeding in the GI tract. They engineered a probiotic strain of E. coli to express a genetic circuit that causes the bacteria to emit light when they encounter heme.

They placed the bacteria into four wells on their custom-designed sensor, covered by a semipermeable membrane that allows small molecules from the surrounding environment to diffuse through. Underneath each well is a phototransistor that can measure the amount of light produced by the bacterial cells and relay the information to a microprocessor that sends a wireless signal to a nearby computer or smartphone. The researchers also built an Android app that can be used to analyse the data.

The researchers tested the ingestible sensor in pigs, demonstrating it could correctly determine whether any blood was present in the stomach.

To help move the technology toward patient use, the researchers plan to reduce the size of the sensor and to study how long the bacteria cells can survive in the digestive tract.

The researchers say the sensors could also be designed to carry multiple strains of bacteria, allowing them to diagnose a variety of conditions.

“Right now, we have four detection sites, but if you could extend it to 16 or 256, then you could have multiple different types of cells and be able to read them all out in parallel, enabling more high-throughput screening,” Assoc Prof. Nadeau concludes.

Author
Bethan Grylls

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